Throughout this application various publications are referred to by number in parentheses. Full citations for these references may be found at the end of the specification. The disclosures of these publications and of all books, patents and patent application publications cited herein are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Treatment of blood losses usually proceeds in a sequence where the initial reduction of blood volume is corrected using plasma expanders. Blood itself is used when the blood loss continues and extends beyond the so called “transfusion trigger”. Outcomes in this process are significantly determined by the restoration of normal microvascular circulation—characterized by the extent to which functional capillary density (FCD) returns to normal (1). FCD is determined as the number of capillaries per unit area of tissue observed with passage of red blood cells (RBCs).
Normal FCD results from the adequate transmission of blood pressure to the periphery and the absence of capillary obstructions due to capillary collapse and abnormal blood cells. Moderate levels of colloidal plasma expansion and hemodilution up to about 50% exchange have no effects on FCD. However if bleeding follows hemodilution the conditions of the organism are significantly affected by the extent of hemodilution and volume loss, a situation described by Van der Linden and Vincent as “tolerance to hemorrhage following hemodilution,” although the effect of different types of hemodiluents have not been investigated (2-4)(5).
Crystalloid and colloidal-based plasma expanders are used in the initial phase of blood volume restoration. New hypotheses are emerging on the relative efficacy of colloid based plasma expanders with significantly different biophysical properties, particularly regarding their viscosity and colloidal osmotic pressure (COP) (2-4). Clinically, human serum albumin (HSA) is also used for plasma expansion in patients (15) but hydroxyethyl starch (HES) is currently the most common clinically used colloid (5-7). Polyethylene glycol (PEG) conjugated human serum albumin (PEG-Alb) (8) has yielded improved microvascular outcomes in experimental resuscitation scenarios (9-14).
This invention provides a method of improving the efficacy of blood transfusions and of improving FCD following transfusions.